THE  ART  OF  MEDICINE

THINKING OUTSIDE the BOX

Discovery consists in seeing what everyone else has seen and thinking what no one else has thought.

—Albert von Szent-Gyorgyi, Nobel Prize-winning physiologist

If practising the art of medicine is principally about bringing more humanity to the doctor-patient relationship, it is not only about humanity. Part of it involves devising creative approaches to diagnosis and treatment, or what I like to call out-of-the-box thinking.

I'm not sure how — or even whether — you can teach future generations of doctors to develop out-of-the-box thinking. The best analogy may be music. You usually need to have years of experience and exposure to the classic forms before you can begin to play jazz. Similarly, in medicine, I would argue that you need to have a broad and deep grasp of basic medicine before you can consider adopting more experimental tactics.

Regardless, it is certainly a skill that physicians young or seasoned would find useful. Quite frequently, disease does not present with the expected or familiar pattern. Especially in an age of multi-system medical problems, disease (and the treatment of it) is becoming a moving target, and physicians need to be agile enough to move with it. I can recall six or seven cases in particular that will help demonstrate what I mean.

Some years ago, the then dean of medicine in Toronto asked me to examine Genevieve, the daughter of a university colleague. Just over 30 years of age, she had long borne the sad burden of neurofibromatosis (NFM), a congenital illness that produces (usually) benign tumours in the brain, spinal cord and other parts of the nervous system.

There is no getting around it: NFM is a nasty disease. These fibrous lesions had already led to a stroke, about a decade earlier, which left Genevieve with partial paralysis. But despite her disability, she was determined to live a normal life. She had earned a certificate in early childhood education, was working part-time in the field and, in her spare time, had managed to become a competent skier.

In addition to the growths on her nervous tissue, Genevieve had developed a large vascular mass — a combination of fibrous tissue and blood vessels — that covered at least half of her trunk. One day, on the ski slopes, she took a nasty spill, falling directly on the vascular mass. She started to bleed profusely. Rushed to Toronto Western Hospital, she had to be administered 35 pints of blood before the bleeding stopped and her equilibrium could be restored. After she was discharged, I was asked to see her.

As if NFM were not enough, she also had an arteriovenous malformation (AVM), an abnormal connection between arteries and veins, likely congenital as well.

I was not a specialist in any of these areas, nor had ever seen this complication of neurofibromatosis before, which I told her. But, after examining her, I did have an out-of-the-box idea that I thought might help. My idea was embolization — a procedure that would implant material, glue or glass particulate, inside the trunk-lesion, which would effectively block the flow of blood. If it worked, it was unlikely the mass would bleed again, even in the event of another accident. In fact, if it worked, then the hardened mass might be amenable to removal by a plastic surgeon.

I was on good terms with Dr. Karel Terbrugge, a colleague who had successfully embolized an AV malformation in the brain of another patient of mine, a much more complicated operation. My reasoning was that if Karel could do it in the brain, he should be able to do it on the skin of the torso.

The family agreed to consider it, while I conferred with my colleague about the degree of difficulty involved. Much to my delight, he was extremely optimistic. It took several sittings, but the procedure worked. Later, a surgeon was able to remove about 80 percent of the mass. Some 13 years later, Genevieve has experienced no further problems from that AV malformation.

Where did my idea come? I knew Karel and the success he had previously had in embolizing other AV malformations. I also knew that unless something was done, Genevieve was at risk of hemorrhaging from the massive amount of blood vessels that covered most of her lower trunk. This led me to embolization treatment, with more than satisfactory results.

ON ANOTHER OCCASION,  I ATTENDED to Joyce, a 45-year-old British woman of Jamaican heritage, who worked for the civil service. She came to see me with a swollen abdomen and a tentative diagnosis -of cirrhosis of the liver, made by her family doctor. I tried to examine her liver and spleen by palpation, but was limited by her pain, which was intense.

I ordered a standard workup, which revealed that her biochemical liver function was normal. Abdominal ultrasound revealed no ascites (excess fluid in the abdomen) and a normal appearing liver. However, a CT scan indicated a blood clot, or thrombosis, in her portal vein, which carries oxygen-depleted blood from the stomach, the intestines, the spleen, the gallbladder and the pancreas to the liver.

Our conclusion was that she was suffering from Budd-Chiari syndrome, which presents with the precise symptoms that were affecting Joyce. The ailment, which is extremely rare, is named after British physician George Budd and Austrian pathologist Hans Chiari. Uncorrected, it leads to portal vein hypertension, which can result in fatal hemorrhage from varices (enlarged blood vessels in the stomach and esophagus). Eventually, we found the genesis of Joyce's malaise — something called an anti-phospholipid antibody.

What happens is that the body's immune system manufactures antibodies that attack a type of fat cell — phospholipids. The damage causes blood clots, like the kind formed in Joyce's portal vein. That, in turn, gave her the pain, the enlarged spleen, portal hypertension and varices.

Then Joyce had a transient ischemic attack (TIA), a kind of mini-stroke. For several hours her arm was paralyzed. The statistics suggest that about 30 percent of people who suffer TIAs experience a full-blown stroke within a year. Moreover, the TIA implied that her condition was not confined to the venous system, but also involved her arterial vessels, a potentially more dangerous situation. She therefore needed preventative therapy against stroke.

So now, I faced a genuine problem. To treat the underlying portal vein thrombosis, we would typically administer an anti-coagulation drug, such as warfarin or heparin. The risk, of course, was that anti-coagulation might precipitate catastrophic bleeding from her massive esophageal varices.

My proposed solution was again based more on instinct than hard science. I wrote her a prescription for Ticlid, an anti-platelet agent. I did not want to use regular anti-coagulation because of the risks posed by her varices and the strong consequential likelihood of more bleeding. At the same time, some type of anti-coagulation was clearly needed. I also chose to add a small dose of warfarin (Coumadin), two milligrams daily.

I was honest about the strategy, telling her there were no clear answers for her condition. That was 13 years ago and, apart from a brief stomach ulcer (successfully treated), Joyce has experienced no bleeding from her varices, no further cerebral ischemic attacks (TIA) and no recurrence of her abdominal thrombosis. I can't say definitively that this strategy prevented any of the more nefarious possibilities, but I can say for sure that this unusual combination (dose-wise) provided a good balance between the risks of bleeding versus the danger of thrombosis (clotting).

A patient's testimony—Joyce C.

I was raised in Jamaica and England and came to Canada in 1972. I worked for a religious-book publisher for many years and then, for 28 years, with the library and archives department of the federal government. I started to have terrible pains in my stomach in 1985, with swelling, weakness and loss of energy. They treated me for ulcers, but that did not work. I've had pain more or less constantly since then. So many doctors, so many hospitals. Not pleasant. One doctor called me the Mystery Woman. I said, "No, I'm not a mystery. It's that science has yet to figure out a lot of things." I'd have pain and swelling at work and have to go home. Once, I was hospitalized for three weeks. I woke up one day and found myself bleeding with needles in my arms. I eventually checked myself out of the hospital. The doctors were preparing to do surgery without knowing why. It was hard for me at work. They thought I was lazy or malingering. I had a few CT scans, but they always came back negative. But I knew from the questions they were asking that what I had was serious. Eventually, my family doctor said he had to send me to a specialist. I was supposed to see a liver doctor but she was unavailable, so I ended up with Dr. Ho Ping Kong.

He did a very thorough examination and decided to admit me, to do more tests. After every test, he would come with the result. He'd sit down and explain what was going on. I was more aware than I would otherwise have been, and it's allowed me to avoid the mistakes that other doctors would have made. My portal veins and my spleen were blocked and my liver was in serious condition, though they assured me it could repair itself. There is no known cause, just the effects. That was October 1994. Then I had a relapse and had to be hospitalized again. It felt like my body was on fire. It was as if you could cook a meal on my body. I was in so much pain I could not squeeze the button to call the nurse. I begged the doctors not to touch me, because of the pain.

Then, two years later, I was at a friend's home. I had spent the day picking peas and later that night I could not move. My whole side was numb. Then after daybreak, it started to tingle. I drove to my family doctor. He couldn't believe it because I'd had a stroke. So I went to see Dr. Ho Ping Kong. That's when he started me on these two medications — Coumadin and Ticlid. Since then, I haven't been hospitalized. I have good days and bad days. I tried to go back to work but I couldn't continue. Stress aggravated the condition and it was a stressful job. Dr. Ho Ping Kong advocated for me so that I could work flexible hours. But eventually, it became too much. I was having anxiety attacks. I could not function. I was afraid to get into an elevator. So I took early retirement in 2000. I've been on the same dosage since then. I have no pain today. I'm blessed.

The medical community will lose a vital doctor when HPK retires. I worry who will replace him, for me and for other patients. I was never treated as a number, but as a human being. He listens. He does not push drugs. He is thorough and he takes all measures to find out what is happening before he acts. It would be good if they could all be like him.

……….

Imagine a condition so painful that it is widely known as the "suicide disease." Such is trigeminal neuralgia (TGN), a neuropathic disorder characterized by acute facial pain. The source of the pain is the trigeminal nerve, the fifth cranial nerve, which branches out to connect with the eye, the ear and the jaw. The actual cause of TGN is unknown. It maybe the result of a virus. It may stem from, some entrapment or compression of part of the nerve. The truth is, we don't know. What we do know is that its victims suffer bouts of intense pain, which can be triggered by effects as random as a gust of wind or a loud sound.

When I saw Anthony, a business executive, for the first time, he had already been a TGN patient for many years. He had been treated initially with gabapentin, a drug originally designed to deal with epilepsy that has been used with some success for neuropathic pain. Unfortunately, he developed side effects and soon had to suspend usage.

Anthony then sought help from neurosurgeons, who performed what is known as a rhizotomy, a procedure that severs the offending nerves. Like many patients who opt for a surgical solution, his symptoms diminished significantly for a number of years. The benefit, however, was finite. Eventually, the pain returned. A second procedure was then performed — an indication, if nothing else, of how debilitating his condition had become. Unfortunately, it was not nearly as successful.

When I saw him, the pain and its consequent disability were severe. Toronto Western Hospital at the time had only recently acquired a Gamma Knife, a device that allows surgeons to aim beams of radiation on very small targets in the brain. The minimally invasive procedure, known as radiosurgery, was invented by the Swedish neurosurgeon Lars Leksell. It delivers a precise, single dose of ionizing radiation without the standard risks of open neurosurgery. Patients are in and out on the same day and usually back to work the same week.

For years, we and many other hospitals sent patients in need of this operation to Sweden. In 2005, we acquired our own in-house Gamma Knife, mainly to deal with acoustic neuromas — tumours that grow on the nerve that connects the brain and the inner ear. But it can be used for TGN, and Anthony had already been booked for the procedure.

Still, he was uncertain. "What happens if it doesn't work?" he asked me. "What alternatives do I have?"

I had no answer, except that he could not be certain that it would not work. I wasn't at all sure what I could contribute of value. He seemed to be good hands, with both neurologists and neurosurgeons. But in the course of conversation, I asked him if anyone had prescribed for him the drug Lyrica, the trade name for an anticonvulsant remedy known as pregabalin. No one had.

Would he be willing to try it, I asked, before committing to radiation via the Gamma Knife? He would.

So I put him on 50 milligrams of Lyrica, once a day, about a third of the usual dose. When he returned, six weeks later, the pain was dramatically reduced — registering a one on a scale of 10, he told me. And his wife even credited me with saving the marriage. Four years later, he is largely pain free. That said, it is still possible that its efficacy will fade with time, and he may yet become a candidate for Gamma Knife surgery. In addition, Anthony will soon need a kidney transplant. He donated one of his kidneys some years ago and, now a diabetic, can no longer function with just one.

A patient's testimony—-Anthony D.

I am 65 years old. I was born in Shanghai and came to Canada at age two. I'm half Portuguese, half English, with some Chinese mixed in there as well. My father was a general practitioner so I had some knowledge of the medical system and how to navigate it, which was ultimately very helpful. I have a master's degree in social work and have run a charitable organization for children for 20 years.

My problem began about 20 years ago. I was having some root canal work done and experienced intense pain in my jaw. My dentist thought the problem was a specific tooth, so he took it out. The pain continued and actually worsened. Then he thought it was another tooth and took that out. In the end, they removed three teeth and I underwent two root canals procedures. I was still in great pain.

I finally got on the right medical track and was diagnosed with trigeminal- neuralgia. It's a strange disease. The nerves near the eye go out of control and shoot out pain signals uncontrollably, like electric shocks. Sometimes, the pain is annoying and sometimes it is totally disabling. No common pain relievers touch it, and weird things trigger it, like wind or even walking. I had a job at that time that required me to speak in front of large groups and I never knew day to day if I could function. But I did. I sucked it up.

Neurologists prescribed some stronger medications, but I was allergic to both of them. Then I saw a neurosurgeon and he eventually performed a rhizotomy, which zaps the nerve. It was high risk, but I felt I had no choice. If they missed the precise spot, I'd have lost muscle control of the eye — unable to blink or walk around with a droop. The surgery worked, but I was left totally numb on that side of the face. You could slap me and I wouldn't have known it.

They told me I should be okay for 10 years, but then the nerve would likely regenerate and they were right. The pain returned. I'd have raging attacks — white light pain — during which I could not open my eyes. I'd sit in a dark room in complete silence waiting for it to pass. I tried meditation techniques and, while they mitigated the pain, they just touched the edge of it. I tried acupuncture, which worked as long as I was lying on the table. But the pain returned immediately afterward. I slept with a mouth guard — no difference.

Sol went back to the neurosurgeon, who was about to retire. I asked him whether he could repeat the procedure. "Oh," he said, "we don't do that anymore. That's barbaric. What we do now is pack a gel on the nerve."

"Okay," I said, "can you do that?"

They tried it and it did nothing. He then sent me to Toronto Western, where they were doing the new Gamma Knife surgery. I was not enthusiastic. They cut into the back of your skull. It works in only two out of three cases. And the effects only last for two years. It was at that point that friends sent me to Dr. Ho Ping Kong, who they called a healer. He examined me and reviewed the various drugs I've tried, without effect. He said, "Have you tried Lyrica?"

"No."

"Well," he said, "it's usually the seventh choice, but if you haven't tried it, what do you have to lose?"

Instant relief. I mean, instant. And no side effects. Because other drugs worked by killing me. I'd fall asleep driving my car. I felt out of control. This drug, Lyrica —once a day, easy. That was four years ago. About every four months, I feel the nerve getting cranky. But the drug blocks the signal. Otherwise, I've been fine. It's amazing to me, because I'd been seeing the top doctors, the top neurologists, the best scientists, who were going down a whole other path. I'd been mangled by dentists and lived through 15 years of hell. It has had a profound impact on my life, and I was looking at severe solutions. The solution x should have been found way upstream. But that is the mystery of medicine. The other doctors are not idiots. They are well informed and well intentioned. But it isn't about science. It's about art, which Ho Ping Kong pays attention to. I now tease him and call him the Great Healer.

……….

Most of the patients I see are sent by specialist or sub-specialist colleagues in the Toronto hospital community. Occasionally, however, I agree to review a case that comes from a general practitioner. Such was the origin of my involvement with Phong, a 37-year-old man Vietnamese man. Six years earlier, Phong had been shot in the stomach by armed men, attempting to rob his computer hardware store. As a result, he lost his spleen, parts of his liver and intestine and suffered damage to his kidney. It was a terrible episode, but he did recover.

A few weeks before I saw him, suffering from urinary frequency and feeling unwell, he went to his local hospital's emergency department. They prescribed a week-long course of antibiotics and sent him home. A week later, he returned, feeling worse. He now complained of insomnia and severe backache. Again, he was given a prescription for antibiotics and again sent home. However, the hospital did organize a CT scan, which proved normal.

Another week passed, and Phong continued to deteriorate. At this point, he visited his family doctor. The pain, he reported, was 10 on a scale of 10 and had begun to radiate into his testicles. Blood work showed a platelet count of almost a million (versus a norm of 400,000), anemia, a sedimentation rate over 100 (compared to a normal level of under 15) and a C-reactive protein reading of 150 (versus a norm of 10-12).

Six weeks had passed from onset to the time that appeared in my office. The poor man was in agony. "This is worse than being shot,'" he told me.

Our working hypothesis was that it was prostatitis, an inflammation of the prostate, and we continued to keep Phong on Cipro, hoping that after six weeks, the drug would finally kill the bacteria. But I was not at ease with the working diagnosis. There were some symptoms of prostatitis that he did not have, and the intense pain in the lower back suggested that something else was going on. My instinct was that the persistent prostatitis could have led to Reiter's syndrome, an arthritic condition that could eventually lead to sacroiliitis.

It took about 10 days, but I arranged an MRI, which showed that he had osteomyelitis of lumbar-sacral spine, a potentially lethal illness. The disc becomes infected and inflamed; in time, the infection can literally eat away your spine. We tried to drain it with a needle, but the cultures proved negative, so we could not actually prove our diagnosis. We knew, of course, that he could still be infected, despite the antibiotics and the normal CT scan.

Nevertheless, we felt confident that we had identified the genesis of his problem and promptly put him on another six-week course of intravenous antibiotics. Without that intervention, Phong could have been a paraplegic in three weeks. Slowly, he improved. We also sent him for a series of immunization shots (pneumococcus, meningococcus, Haemophilus). What we should have realized sooner is that, with his spleen removed, he was vulnerable to invasion by encapsulated and other organisms. Still, by thinking outside the box, I'm quite sure that we literally saved his life.

Phong's spleen reminds me of another instructive out-of-the-box dossier. For almost 30 years, I or a senior colleague has presided over Morning Report — an 8 a.m. session during which a designated medical intern or resident presents a new patient case, from the previous night's inventory in the emergency department. The challenge for those assembled is to use the details of the case to make the right diagnosis. The tacit competition yielded some very lively discussions.

When I chair the meeting, I typically adopt a form of the Socratic method that I learned many decades ago at my Jesuit college in Jamaica. I provide cryptic clues about the case under discussion — clues often drawn from the morning news, weather and occasionally sports reports. Successive waves of medical students and residents have learned that, to prepare for my appearances, they would be well advised to familiarize themselves with current events. My goal is not simply to enliven the proceedings, but to make the learning interactive and more memorable.

On one particular morning, one of the residents told us about Josh, a 22-year-old second-year medical student and hockey player at the University of Toronto. The previous weekend, the University of Toronto team had travelled to Quebec City to play against Universite Laval. That involved two 12-hour bus rides, interrupted only by the game, a meal and a short night's sleep. During the game, Josh was crushed into the boards, but not seriously hurt.

Nevertheless, soon after returning home, he was feeling enough pain in the left part of his chest to visit the emergency department. He reported that it hurt to take a deep breath and he also had a sore throat. The first instinct of the attending staff was that, because of his long bus ride and perhaps somewhat dehydrated because of the hockey game, this was likely a pulmonary embolism — a blood clot in the lung. So they immediately administered the blood thinner heparin.

"But he's a healthy young man," I told the Morning Report. "There was no fracture. So, despite the long bus ride, how likely is it that he'd develop a pulmonary embolism? What else might it be? What else is there in that region, structurally?"

"The spleen," someone said.

"So could it be a ruptured spleen? What would rupture the spleen?"

"The injury during the game," came the answer. "Being pushed against the boards."

"But the injury was minor," I reminded them. "Who else gets a ruptured spleen?"

"People with leukemia," one resident suggested.

"That's correct. And if you have leukemia, you are frequently what?" No one had the answer, so I provided it. "You are thrombocytopenic," meaning that you are deficient in blood platelets and prone to bleeding. -^

"But again, he's otherwise healthy, with no other symptoms," I said. "Any other suggestions?"

"Mononucleosis."

"Aha," I said. "And what happens to the spleen then?"

"It gets larger and softer and it may rupture."

"What else might suggest mononucleosis?"

"The sore throat."

"Very good. So we have put him on heparin to promote bleeding when, in fact, if he has mononucleosis and a ruptured spleen, he is already bleeding. He could bleed to death."

Needless to say, this reversal of the verdict already arrived at provoked some concern. A ct scan and ultrasound were quickly arranged, which confirmed the ruptured spleen. Blood tests later verified mononucleosis.

You might think there should have been more evidence of bleeding, but this is where anatomical and pathological knowledge is critical. The spleen may rupture into the peritoneal cavity and produce massive volume depletion, shock and abdominal pain — obvious signs of bleeding. But the patient may also experience what we call a subcapsular hemorrhage, where the blood is contained, at least temporarily, by a fibrous covering; it may rupture later — or not. In the first instance, an emergency splenectomy — removal of the spleen — would be needed. Fortunately, the latter was what occurred with Josh. We immediately stopped the heparin and watched him carefully for the next several days. He soon recovered.

One day about four our years ago, I had a telephone call from Paul, a successful businessman in his mid-60s and a longtime patient of mine. He'd had some heart issues a decade earlier and, even before all the evidentiary studies about statins were in, I had started him on a course of these cholesterol-reducing drugs. When he called, Paul was on business in Florida. He'd being exercising, he said, and had experienced some angina-like chest pain.

"I had it just after I started, but then it disappeared," he said. "I worked through it. I did my usual five kilometres on the treadmill."

This is a familiar condition to cardiologists — so-called walkthrough angina. If the heart makes a gradual adaptation to the increased stress of exercise, the pain subsides. The common assumption is that this condition constitutes so-called stable angina — nothing to worry about immediately. If the pain does not abate, then it is labelled unstable angina, and the patient is likely a candidate for a battery of tests, including, if necessary, an angiogram.

Paul was looking for reassurance that nothing serious was wrong. "I asked some doctors here and they said it's probably fine. What do you think?"

My response was instinctive. "I don't think-HLt's okay. When are you coming home?"

"Tonight."

"I'm going to see how soon we can get you an appointment with a cardiologist. I'll call you back in 10 minutes."

At 8 a.m. the next morning, Paul was given a stress test at Toronto General Hospital. At 8:30, he went into the angio suite to have an angiogram. A few hours later, I received a call from his brother-in-law, a doctor, thanking me. The procedure had found a significant arterial blockage. Angioplasty — a balloon stent — had been performed.

Symptoms of angina are often difficult to read. Heart pain can be a great mimic. It can manifest itself as an upset stomach, as hearburn, as nausea, as a pain in the jaw, as profuse sweating, even on occasion as an acute pain in the thumb — and nothing more. Sometimes, angina comes on in the wee hours of the morning — 3 or 4 a.m. — though we aren't sure why. Perhaps 70 percent of the time, it presents with the classic symptoms of squeezing and pressure in the chest, with a feeling of impending doom. But about a third of the time it takes other forms.

It would have been easy for me to assume, as the doctors Paul consulted in Florida had, that he was basically fine, because he had managed to work through the initial treadmill pain. My instinct — my willingness to think outside the box — told me this might be serious. I'm delighted to report that because of his stents, Paul has been free of angina-like pain ever since.

By now, it is probably clear that many diseases fall into the challenging realm of I-can't-prove-you-have-it-and-you-can't-prove-you-don't. The only way to treat the illness is to devise a therapeutic trial for a single patient, testing various medications until we find one that-effectively eliminates or reduces the symptoms. Even then, of course, we never know definitively whether we have relieved or cured the ailment we suspected. But we know something more important — that we have helped the patient resume a normal life.

The abdominal migraine — an offshoot of the classic migraine headache — is one of these problematic conditions. It is neither rare nor common. The medical literature suggests that it is a phenomenon principally seen in children, but that has not been my experience. Every few years, I meet an adult patient who has its symptoms — abdominal pain, nausea and lethargy. The first step is to determine if anything more serious might be involved.

Not long ago, I treated Sonya, a 35-year-old Hungarian woman, who had been referred by her family physician. She had been unwell for about six months, complaining of non-spec nausea and fatigue. The condition had begun to impinge on normally active lifestyle.

I ordered a limited workup to check for anemia or peptic ulcer. These proved negative, as had an endoscopy— a probe of the upper gastrointestinal tract — arranged earlier. I also determined that Sonya had no kidney or brain disease. But when I took her history, she allowed that she had in the past experienced classical migraines with flashing lights and sensitivity to noise. I explained that it was possible her migraine was affecting her stomach, and that I wanted to prescribe a beta blocker, propranolol. Beta blockers are more commonly used to treat cardiac patients, but a small dose of 10 milligrams twice daily has also been shown to be preventative of migraine. Three months later, she returned, with no signs of nausea. Again, I could not prove my diagnosis was correct, but she was clearly improved — and has remained so — without exposing her to invasive tests, significant risk or medications with more pernicious side effects.

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